-First of Two Planned Trials Combining ADCETRIS
and Opdivo Under Clinical Collaboration Agreement with
Bristol-Myers Squibb-
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that it has
initiated a phase 1/2 clinical trial of ADCETRIS (brentuximab
vedotin) in combination with Opdivo (nivolumab) for patients with
relapsed or refractory Hodgkin lymphoma (HL) after failure of
frontline treatment. The trial is being conducted under a
previously announced clinical trial collaboration agreement with
Bristol-Myers Squibb Company (NYSE:BMY). ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30, a defining marker
of classical HL, which combines the targeting ability of a
monoclonal antibody with a highly potent cell-killing agent. Opdivo
is a human antibody that targets and inhibits the programmed death
receptor-1 (PD-1), resulting in T-cell activation. Opdivo is part
of a new class of cancer immunotherapy treatments known as
checkpoint inhibitors, which are designed to harness the body’s own
immune system in fighting cancer by targeting distinct regulatory
components of the immune system. A second trial under the
collaboration is planned to begin later in 2015 for relapsed or
refractory B-cell and T-cell non-Hodgkin lymphoma (NHL), including
diffuse large B-cell lymphoma (DLBCL).
“This is the first corporate-sponsored clinical trial to
evaluate ADCETRIS combined with a checkpoint inhibitor to determine
if the combination can improve patient outcomes,” said Jonathan
Drachman, M.D., Chief Medical Officer and Executive Vice President,
Research and Development. “The trial supports our strategy to
establish ADCETRIS as the foundation of care for CD30-expressing
malignancies, and to test novel combinations that could benefit
patients. We are executing a broad clinical program with ADCETRIS
to potentially expand into earlier lines of therapy and new
indications, including the ECHELON-1 trial in frontline Hodgkin
lymphoma, the ECHELON-2 trial in frontline mature T-cell lymphoma,
the ALCANZA trial in cutaneous T-cell lymphoma and both ongoing and
planned trials in diffuse large B-cell lymphoma.”
The phase 1/2 open-label trial will enroll relapsed or
refractory HL patients who have failed frontline therapy. The
primary objective is to assess the safety and antitumor activity of
ADCETRIS in combination with Opdivo. After completion of four
cycles of combination therapy, patients are eligible to undergo
autologous stem cell transplant (ASCT). Patients at high risk of
relapse or progression following ASCT will be eligible to receive
ADCETRIS in the commercial setting. All patients will be assessed
for progression-free survival after ASCT. The trial is being
conducted at multiple centers in the United States and is designed
to enroll up to approximately 60 patients.
ADCETRIS is not currently approved for the treatment of
second-line, transplant eligible HL or for the treatment of NHL
other than relapsed systemic anaplastic large cell lymphoma. Opdivo
is currently not approved for the treatment of lymphoma.
About ADCETRIS® (Brentuximab Vedotin)
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody
attached by a protease-cleavable linker to a microtubule disrupting
agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’
proprietary technology. The ADC employs a linker system that is
designed to be stable in the bloodstream but to release MMAE upon
internalization into CD30-expressing tumor cells.
ADCETRIS for intravenous injection has received approval from
the FDA for three indications: (1) regular approval for the
treatment of patients with classical HL after failure of autologous
hematopoietic stem cell transplantation (auto-HSCT) or after
failure of at least two prior multi-agent chemotherapy regimens in
patients who are not auto-HSCT candidates, (2) regular approval for
the treatment of classical HL patients at high risk of relapse or
progression as post-auto-HSCT consolidation, and (3) accelerated
approval for the treatment of patients with systemic anaplastic
large cell lymphoma (sALCL) after failure of at least one prior
multi-agent chemotherapy regimen. The sALCL indication is approved
under accelerated approval based on overall response rate.
Continued approval for the sALCL indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials. Health Canada granted ADCETRIS approval with conditions for
relapsed or refractory HL and sALCL.
ADCETRIS was granted conditional marketing authorization by the
European Commission in October 2012 for two indications: (1) for
the treatment of adult patients with relapsed or refractory
CD30-positive HL following autologous stem cell transplant (ASCT),
or following at least two prior therapies when ASCT or multi-agent
chemotherapy is not a treatment option, and (2) the treatment of
adult patients with relapsed or refractory sALCL. ADCETRIS has
received marketing authorization by regulatory authorities in more
than 55 countries. See important safety information below.
Seattle Genetics and Takeda Pharmaceutical Company Limited
(Takeda) are jointly developing ADCETRIS. Under the terms of the
collaboration agreement, Seattle Genetics has U.S. and Canadian
commercialization rights and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seattle Genetics and Takeda are
funding joint development costs for ADCETRIS on a 50:50 basis,
except in Japan where Takeda is solely responsible for development
costs.
About Lymphoma
Lymphoma is a general term for a group of cancers that originate
in the lymphatic system. There are two major categories of
lymphoma: HL and NHL. HL is distinguished from other types of
lymphoma by the presence of one characteristic type of cell, known
as the Reed-Sternberg cell. The Reed-Sternberg cell generally
expresses CD30. NHL is further categorized into indolent
(low-grade) or aggressive, including DLBCL. DLBCL is the most
common type of NHL.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the
development and commercialization of innovative antibody-based
therapies for the treatment of cancer. Seattle Genetics is leading
the field in developing antibody-drug conjugates (ADCs), a
technology designed to harness the targeting ability of antibodies
to deliver cell-killing agents directly to cancer cells. The
company’s lead product, ADCETRIS® (brentuximab vedotin) is a
CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical
Company Limited, is commercially available in more than 55
countries, including the U.S., Canada, Japan and members of the
European Union. Additionally, ADCETRIS is being evaluated broadly
in more than 30 ongoing clinical trials in CD30-expressing
malignancies. Seattle Genetics is also advancing a robust pipeline
of clinical-stage programs, including SGN-CD19A, SGN-CD33A,
SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. Seattle
Genetics has collaborations for its ADC technology with a number of
leading biotechnology and pharmaceutical companies, including
AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech,
GlaxoSmithKline and Pfizer. More information can be found at
www.seattlegenetics.com.
ADCETRIS (brentuximab vedotin) U.S. Important Safety
Information
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death can occur in patients
receiving ADCETRIS® (brentuximab vedotin).
Contraindication
ADCETRIS is contraindicated with concomitant bleomycin due to
pulmonary toxicity (e.g., interstitial infiltration and/or
inflammation).
Warnings and Precautions
- Peripheral neuropathy: ADCETRIS
treatment causes a peripheral neuropathy that is predominantly
sensory. Cases of peripheral motor neuropathy have also been
reported. ADCETRIS-induced peripheral neuropathy is cumulative.
Monitor patients for symptoms of neuropathy, such as hypoesthesia,
hyperesthesia, paresthesia, discomfort, a burning sensation,
neuropathic pain or weakness and institute dose modifications
accordingly.
- Anaphylaxis and infusion
reactions: Infusion-related reactions, including anaphylaxis,
have occurred with ADCETRIS. Monitor patients during infusion. If
an infusion-related reaction occurs, interrupt the infusion and
institute appropriate medical management. If anaphylaxis occurs,
immediately and permanently discontinue the infusion and administer
appropriate medical therapy.
- Hematologic toxicities:
Prolonged (≥1 week) severe neutropenia and Grade 3 or 4
thrombocytopenia or anemia can occur with ADCETRIS. Febrile
neutropenia has been reported with ADCETRIS. Monitor complete blood
counts prior to each dose of ADCETRIS and consider more frequent
monitoring for patients with Grade 3 or 4 neutropenia. Monitor
patients for fever. If Grade 3 or 4 neutropenia develops, consider
dose delays, reductions, discontinuation, or G-CSF prophylaxis with
subsequent doses.
- Serious infections and opportunistic
infections: Infections such as pneumonia, bacteremia, and
sepsis or septic shock (including fatal outcomes) have been
reported in patients treated with ADCETRIS. Closely monitor
patients during treatment for the emergence of possible bacterial,
fungal or viral infections.
- Tumor lysis syndrome: Closely
monitor patients with rapidly proliferating tumor and high tumor
burden.
- Increased toxicity in the presence
of severe renal impairment: The frequency of ≥Grade 3 adverse
reactions and deaths was greater in patients with severe renal
impairment compared to patients with normal renal function. Avoid
the use of ADCETRIS in patients with severe renal impairment.
- Increased toxicity in the presence
of moderate or severe hepatic impairment: The frequency of
≥Grade 3 adverse reactions and deaths was greater in patients with
moderate or severe hepatic impairment compared to patients with
normal hepatic function. Avoid the use of ADCETRIS in patients with
moderate or severe hepatic impairment.
- Hepatotoxicity: Serious cases of
hepatotoxicity, including fatal outcomes, have occurred with
ADCETRIS. Cases were consistent with hepatocellular injury,
including elevations of transaminases and/or bilirubin, and
occurred after the first dose of ADCETRIS or rechallenge.
Preexisting liver disease, elevated baseline liver enzymes, and
concomitant medications may also increase the risk. Monitor liver
enzymes and bilirubin. Patients experiencing new, worsening, or
recurrent hepatotoxicity may require a delay, change in dose, or
discontinuation of ADCETRIS.
- Progressive multifocal
leukoencephalopathy (PML): JC virus infection resulting in PML
and death has been reported in ADCETRIS-treated patients. First
onset of symptoms occurred at various times from initiation of
ADCETRIS therapy, with some cases occurring within 3 months of
initial exposure. In addition to ADCETRIS therapy, other possible
contributory factors include prior therapies and underlying disease
that may cause immunosuppression. Consider the diagnosis of PML in
any patient presenting with new-onset signs and symptoms of central
nervous system abnormalities. Hold ADCETRIS if PML is suspected and
discontinue ADCETRIS if PML is confirmed.
- Pulmonary Toxicity: Events of
noninfectious pulmonary toxicity including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome,
some with fatal outcomes, have been reported. Monitor patients for
signs and symptoms of pulmonary toxicity, including cough and
dyspnea. In the event of new or worsening pulmonary symptoms, hold
ADCETRIS dosing during evaluation and until symptomatic
improvement.
- Serious dermatologic reactions:
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
(TEN), including fatal outcomes, have been reported with ADCETRIS.
If SJS or TEN occurs, discontinue ADCETRIS and administer
appropriate medical therapy.
- Embryo-fetal toxicity: Fetal
harm can occur. Advise pregnant women of the potential hazard to
the fetus.
Most Common Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients with
relapsed classical HL and sALCL in two uncontrolled single-arm
trials. Across both trials, the most common adverse reactions
(≥20%), regardless of causality, were neutropenia, peripheral
sensory neuropathy, fatigue, nausea, anemia, upper respiratory
tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough
and vomiting.
ADCETRIS was studied in 329 patients with classical HL at high
risk of relapse or progression post-auto-HSCT in a
placebo-controlled randomized trial. The most common adverse
reactions (≥20%) in the ADCETRIS-treatment arm (167 patients),
regardless of causality, were neutropenia, peripheral sensory
neuropathy, thrombocytopenia, anemia, upper respiratory tract
infection, fatigue, peripheral motor neuropathy, nausea, cough, and
diarrhea.
Drug Interactions:
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp
inhibitors, has the potential to affect the exposure to monomethyl
auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients
with moderate or severe hepatic impairment or severe renal
impairment. Avoid use.
For additional Important Safety Information, including Boxed
WARNING, please see the full Prescribing Information for ADCETRIS
at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.
Forward-Looking Statements
Certain of the statements made in this press release are
forward-looking, such as those, among others, relating to the
future potential therapeutic uses of ADCETRIS (including in
combination with Opdivo) and future clinical and regulatory
progress. Actual results or developments may differ materially from
those projected or implied in these forward-looking statements.
Factors that may cause such a difference include risks related to
adverse clinical results associated with the use of ADCETRIS or
Opdivo (or the combination), the failure of the companies to
continue their collaboration or execute on the planned clinical
trials or adverse regulatory action. More information about the
risks and uncertainties faced by Seattle Genetics is contained
under the caption “Risk Factors” included in Exhibit 99.1 to the
company’s Current Report on Form 8-K filed with the Securities and
Exchange Commission on September 9, 2015. Seattle Genetics
disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise.
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version on businesswire.com: http://www.businesswire.com/news/home/20151007005370/en/
Seattle Genetics, Inc.Investors:Peggy Pinkston,
425-527-4160ppinkston@seagen.comorMedia:Tricia Larson,
425-527-4180tlarson@seagen.com
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